MYOCARDIAL GLUCOSE-UTILIZATION - FAILURE OF ADENOSINE TO ALTER IT AND INHIBITION BY THE ADENOSINE ANALOG N-6-(L-2-PHENYLISOPROPYL)ADENOSINE

被引:35
作者
DALE, WE
HALE, CC
KIM, HD
ROVETTO, MJ
机构
[1] UNIV MISSOURI,DALTON RES CTR,DEPT VET BIOMED SCI,COLUMBIA,MO 65211
[2] UNIV MISSOURI,DALTON RES CTR,DEPT PHYSIOL,COLUMBIA,MO 65211
[3] UNIV MISSOURI,DALTON RES CTR,DEPT PHARMACOL,COLUMBIA,MO 65211
[4] WASHINGTON UNIV,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63130
关键词
N-6-(L-2-PHENYLISOPROPYL)ADENOSINE; GLUCOSE UTILIZATION; ADENOSINE; PIA;
D O I
10.1161/01.RES.69.3.791
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effects of adenosine and the nonmetabolizable adenosine analogue N6-(L-2-phenylisopropyl) adenosine (PIA) on glucose transport or metabolism were determined in purified myocardial sarcolemmal vesicles, isolated cardiocytes, and perfused hearts. Adenosine (100-mu-M) did not affect hexose transport in myocytes. Also, adenosine deaminase, added to metabolize adenosine to inosine, did not alter transport of hexose into myocytes regardless of whether or not insulin was present. In contrast, PIA effectively inhibited 3-O-methyl-D-glucose uptake in myocytes even during insulin stimulation. PIA inhibited D-glucose-specific transport in both rat and bovine cardiac sarcolemmal vesicles (K(i) = 26-mu-M at [D-glucose] = 5 mM). However, insulin did not affect glucose transport in sarcolemmal vesicles, which implies that receptor-coupled processes probably are not intact in this preparation. Thus, inhibition of PIA may not be receptor mediated. Also, PIA inhibited binding of cytochalasin B to bovine cardiac sarcolemmal vesicles, which supports the idea that PIA inhibits glucose flux by binding to the glucose transporter. To determine if adenosine altered glucose metabolism rather than transport, we measured the rate of (H2O)-H-3 production from metabolism of D-[2-H-3]glucose in paced rat hearts ([D-glucose] = 5.5 mM, [pyruvate] = 0.2 mM) perfused with a range of PIA or adenosine concentrations with or without 0.01-mu-M insulin. Adenosine (0.01-100-mu-M) in the presence or absence of insulin increased coronary flow but did not change glycolytic rates. Similar results were obtained with PIA (no insulin) rather than adenosine in the perfusate. However, with glucose as the only exogenous substrate, 100-mu-M PIA inhibited glycolysis by approximately 50%. It also prevented hypoxia-induced increase in glycolysis in hearts perfused with glucose and pyruvate. We conclude that adenosine and PIA do not affect glycolysis in hearts perfused with pyruvate as an exogenous substrate but that PIA inhibits glucose utilization if glucose use is limited by membrane transport, such as with glucose as the sole exogenous substrate or during hypoxia. PIA affects glucose transport as it inhibits this process in cardiomyocytes and sarcolemmal vesicles by binding to the glucose transport molecule.
引用
收藏
页码:791 / 799
页数:9
相关论文
共 42 条